| First Author | Li J | Year | 2015 |
| Journal | PLoS One | Volume | 10 |
| Issue | 3 | Pages | e0118480 |
| PubMed ID | 25738607 | Mgi Jnum | J:357010 |
| Mgi Id | MGI:6248383 | Doi | 10.1371/journal.pone.0118480 |
| Citation | Li J, et al. (2015) Reciprocal interaction of Wnt and RXR-alpha pathways in hepatocyte development and hepatocellular carcinoma. PLoS One 10(3):e0118480 |
| abstractText | Genomic analysis of human hepatocellular carcinoma (HCC) is potentially confounded by the differentiation state of the hepatic cell-of-origin. Here we integrated genomic analysis of mouse HCC (with defined cell-of-origin) along with normal development. We found a major shift in expression of Wnt and RXR-alpha pathway genes (up and down, respectively) coincident with the transition from hepatoblasts to hepatocytes. A combined Wnt and RXR-alpha gene signature categorized HCCs into two subtypes (high Wnt, low RXR-alpha and low Wnt, high RXR-alpha), which matched cell-of-origin in mouse models and the differentiation state of human HCC. Suppression of RXR-alpha levels in hepatocytes increased Wnt signaling and enhanced tumorigenicity, whereas ligand activation of RXR-alpha achieved the opposite. These results corroborate that there are two main HCC subtypes that correspond to the degree of hepatocyte differentation and that RXR-alpha, in part via Wnt signaling, plays a key functional role in the hepatocyte-like subtype and potentially could serve as a selective therapeutic target. |
